Whole-Transcriptome Reveals Autophagy-Related Competitive Endogenous RNA Network Regulating Angiogenic Differentiation of Dental Pulp Stem Cells in Pulpitis

Background Early pulpitis often accompanies local microcirculation disorders. Autophagy plays a regulatory role in angiogenesis in various diseases, but its role in angiogenesis of pulpitis remains unclear. Methods RNA sequencing was performed on dental pulp stem cells (DPSCs) before and after angiogenic differentiation induction to screen differentially expressed (DE) messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA). Core genes were identified in combination with the autophagy-related gene set and a competitive endogenous RNA (ceRNA) network was constructed. The effects of the autophagy activator rapamycin on inflammation and angiogenesis were observed through a mouse pulpitis model. Results RNA sequencing analysis identified 2013 DE-lncRNAs, 5089 DE-mRNAs, and 148 DE-miRNAs. Enrichment analysis revealed that the differentially expressed genes (DEGs) were significantly enriched in autophagy-related pathways such as 'Autophagy-animal', and 'FoxO signalling pathway'. By combining the autophagy gene set and conducting Protein-Protein Interaction (PPI) network analysis, Molecular Complex Detection (MCODE) algorithm and Maximal Clique Centrality (MCC) algorithm, CASP3, DDIT3, ATF6, and ERN1 were determined as hub genes. Based on the ceRNA theory, a regulatory network containing 15 lncRNAs, 4 miRNAs, and 4 mRNAs was successfully constructed. In the animal experiments, the rapamycin intervention group showed reduced IL-18, mTOR, and p62 expression and significantly increased VEGF and ET expression. Conclusion This study screened out the key RNAs related to autophagy in the angiogenic differentiation of DPSCs, constructed the ceRNA regulatory network under pulpitis, providing new clues for understanding the relationship between autophagy on angiogenesis and also offering a preliminary theoretical basis for targeted intervention.